EzCatDB: M00216

DB codeM00216
RLCP classification1.13.30000.41
CATH domainDomain 13.90.70.-
Domain 24.10.90.10
Domain 32.60.120.10
Domain 42.60.120.10
Domain 52.60.120.10
Domain 6-.-.-.-
Domain 7-.-.-.-
Domain 8-.-.-.-
Domain 9-.-.-.-
Domain 10-.-.-.-
Domain 11-.-.-.-
Domain 12-.-.-.-
Domain 132.40.10.10Catalytic domain
Domain 142.40.10.10Catalytic domain
Domain 153.90.-.-
Domain 163.30.-.-
Domain 171.20.-.-
Domain 181.10.-.-
E.C.3.4.22.46,3.6.1.15,3.4.22.28,2.7.7.48
CSA2bhg

CATH domainRelated DB codes (homologues)
2.40.10.10M00139,D00214,M00167,D00426,M00133,D00428,D00429,D00430,D00431,D00432,D00433,D00434,D00435,D00424,M00209,D00194,D00197,D00211,D00212,D00216,M00212,D00224,D00497,M00217,D00528,M00152,M00155,M00157,M00181,T00074
2.60.120.10S00145,S00155,T00255,T00101

Enzyme Name
Swiss-protKEGG

P03306
Protein nameGenome polyproteinL-peptidase
   (EC 3.4.22.46)
nucleoside-triphosphatase
   (EC 3.6.1.15)
nucleoside triphosphate phosphohydrolase
   (EC 3.6.1.15)
nucleoside-5-triphosphate phosphohydrolase
   (EC 3.6.1.15)
nucleoside 5-triphosphatase
   (EC 3.6.1.15)
picornain 3C
   (EC 3.4.22.28)
picornavirus endopeptidase 3C
   (EC 3.4.22.28)
poliovirus protease 3C
   (EC 3.4.22.28)
rhinovirus protease 3C
   (EC 3.4.22.28)
foot-and-mouth protease 3C
   (EC 3.4.22.28)
poliovirus proteinase 3C
   (EC 3.4.22.28)
rhinovirus proteinase 3C
   (EC 3.4.22.28)
coxsackievirus 3C proteinase
   (EC 3.4.22.28)
foot-and-mouth-disease virus proteinase 3C
   (EC 3.4.22.28)
3C protease
   (EC 3.4.22.28)
3C proteinase
   (EC 3.4.22.28)
cysteine proteinase 3C
   (EC 3.4.22.28)
hepatitis A virus 3C proteinase
   (EC 3.4.22.28)
protease 3C
   (EC 3.4.22.28)
tomato ringspot nepovirus 3C-related protease
   (EC 3.4.22.28)
RNA-directed RNA polymerase
   (EC 2.7.7.48)
RNA nucleotidyltransferase (RNA-directed)
   (EC 2.7.7.48)
RNA nucleotidyltransferase (RNA-directed)
   (EC 2.7.7.48)
RNA-dependent ribonucleate nucleotidyltransferase
   (EC 2.7.7.48)
3D polymerase
   (EC 2.7.7.48)
PB1 proteins
   (EC 2.7.7.48)
PB2 proteins
   (EC 2.7.7.48)
phage f2 replicase
   (EC 2.7.7.48)
polymerase L
   (EC 2.7.7.48)
Q-beta replicase
   (EC 2.7.7.48)
phage f2 replicase
   (EC 2.7.7.48)
ribonucleic acid replicase
   (EC 2.7.7.48)
ribonucleic acid-dependent ribonucleate nucleotidyltransferase
   (EC 2.7.7.48)
ribonucleic acid-dependent ribonucleic acid polymerase
   (EC 2.7.7.48)
ribonucleic replicase
   (EC 2.7.7.48)
ribonucleic synthetase
   (EC 2.7.7.48)
RNA replicase
   (EC 2.7.7.48)
RNA synthetase
   (EC 2.7.7.48)
RNA transcriptase
   (EC 2.7.7.48)
RNA-dependent ribonucleate nucleotidyltransferase
   (EC 2.7.7.48)
RDRP
   (EC 2.7.7.48)
RNA-dependent RNA polymerase
   (EC 2.7.7.48)
RNA-dependent RNA replicase
   (EC 2.7.7.48)
transcriptase
   (EC 2.7.7.48)
SynonymsNone
ContainsLeader protease
(Lpro)
   EC 3.4.22.46
Protein VP0 VP4-VP2
Protein VP4 Virion protein 4 P1A
Protein VP2 Virion protein 2 P1B
Protein VP3 Virion protein 3 P1C
Protein VP1 Virion protein 1 P1D
Protein 2A
(P2A)
P52
Protein 2B
(P2B)
Protein 2C
(P2C)
   EC 3.6.1.15
Protein 3A
(P3A)
Protein 3B-1
(P3B-1)
Genome-linked protein VPg1
Protein 3B-2
(P3B-2)
Genome-linked protein VPg2
Protein 3B-3
(P3B-3)
Genome-linked protein VPg3
Picornain 3C
   EC 3.4.22.28
Protease 3C
(P3C)
Protease P20B
RNA-directed RNA polymerase 3D-POL
(P3D-POL)
   EC 2.7.7.48
P56A

KEGG pathways
MAP codePathwaysE.C.
MAP00230Purine metabolism3.6.1.15,2.7.7.48
MAP00730Thiamine metabolism3.6.1.15

Swiss-prot:Accession NumberP03306
Entry namePOLG_FMDV1
ActivityAutocatalytically cleaves itself from the polyprotein of the foot-and-mouth disease virus by hydrolysis of a Lys-|-Gly bond, but then cleaves host cell initiation factor eIF- 4G at bonds -Gly-|-Arg- and -Lys-|-Arg-.,NTP + H(2)O = NDP + phosphate.,Selective cleavage of Gln-|-Gly bond in the poliovirus polyprotein. In other picornavirus reactions Glu may be substituted for Gln, and Ser or Thr for Gly.,Nucleoside triphosphate + RNA(n) = diphosphate + RNA(n+1).
Subunit
Subcellular locationProtein VP2: Virion. Cytoplasm (Potential).,Protein VP3: Virion. Cytoplasm (Potential).,Protein VP1: Virion. Cytoplasm (Potential).,Protein 2B: Cytoplasmic vesicle membrane, Peripheral membrane protein, Cytoplasmic side (Potential). Note=Probably localizes to the surface of intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication. These vesicles are derived from the endoplasmic reticulum (By similarity).,Protein 2C: Cytoplasmic vesicle membrane, Peripheral membrane protein, Cytoplasmic side (Potential). Note=Probably localizes to the surface of intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication. These vesicles are derived from the endoplasmic reticulum (By similarity).,Protein 3A: Cytoplasmic vesicle membrane, Peripheral membrane protein, Cytoplasmic side (Potential). Note=Probably localizes to the surface of intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication. These vesicles are derived from the endoplasmic reticulum (By similarity).,Protein 3B-1: Virion (Potential).,Protein 3B-2: Virion (Potential).,Protein 3B-3: Virion (Potential).,Picornain 3C: Cytoplasm (Potential).,RNA-directed RNA polymerase 3D-POL: Cytoplasmic vesicle membrane, Peripheral membrane protein, Cytoplasmic side (Potential). Note=Probably localizes to the surface of intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication. These vesicles are derived from the endoplasmic reticulum (By similarity).
Cofactor


SubstratesProducts
KEGG-idC00017C00001C00201C00046C00017C00012C00454C00009C00046C00013
E.C.3.4.22.46,3.4.22.283.4.22.46,3.4.22.28,3.6.1.153.6.1.15,2.7.7.482.7.7.483.4.22.46,3.4.22.283.4.22.46,3.4.22.283.6.1.153.6.1.152.7.7.482.7.7.48
CompoundProteinH2ONucleoside triphosphateRNA(n)ProteinPeptideNucleoside diphosphatePhosphateRNA(n+1)Diphosphate
Typepeptide/proteinH2Onucleotidenucleic acidspeptide/proteinpeptide/proteinnucleotidephosphate group/phosphate ionnucleic acidsphosphate group/phosphate ion
1zba4Unbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1zbe4Unbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1zba2Unbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1zbe2Unbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1zba3Unbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1zbe3Unbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1zba1Unbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1zbe1Unbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2bhgA1Unbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2bhgB1Unbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2bhgA2Unbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2bhgB2Unbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound

Active-site residues
resource
Swiss-prot;P03306 & literature [9]
pdbCatalytic residuesMain-chain involved in catalysiscomment
1zba4


1zbe4


1zba2


1zbe2


1zba3


1zbe3


1zba1


1zbe1


2bhgA1HIS 46;ASP 84


2bhgB1HIS 46;ASP 84


2bhgA2       
GLY 161
mutant C163A
2bhgB2       
GLY 161
mutant C163A

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[2]p.110
[9]p.11524

references
[1]
PubMed ID3186696
JournalProc Natl Acad Sci U S A
Year1988
Volume85
Pages7872-6
AuthorsBazan JF, Fletterick RJ
TitleViral cysteine proteases are homologous to the trypsin-like family of serine proteases: structural and functional implications.
[2]
PubMed ID2645167
JournalFEBS Lett
Year1989
Volume243
Pages103-14
AuthorsGorbalenya AE, Donchenko AP, Blinov VM, Koonin EV
TitleCysteine proteases of positive strand RNA viruses and chymotrypsin-like serine proteases. A distinct protein superfamily with a common structural fold.
[3]
PubMed ID8320292
JournalJ Chem Inf Comput Sci
Year1993
Volume33
Pages345-9
AuthorsArad D, Kreisberg R, Shokhen M
TitleStructural and mechanistic aspects of 3C proteases from the Picornavirus family.
[4]
PubMed ID8164744
JournalNature
Year1994
Volume369
Pages72-6
AuthorsAllaire M, Chernaia MM, Malcolm BA, James MN
TitlePicornaviral 3C cysteine proteinases have a fold similar to chymotrypsin-like serine proteinases.
[5]
PubMed ID7491782
JournalVirology
Year1995
Volume213
Pages581-9
AuthorsGrubman MJ, Zellner M, Bablanian G, Mason PW, Piccone ME
TitleIdentification of the active-site residues of the 3C proteinase of foot-and-mouth disease virus.
[6]
PubMed ID9060667
JournalJ Virol
Year1997
Volume71
Pages3062-8
AuthorsGosert R, Dollenmaier G, Weitz M
TitleIdentification of active-site residues in protease 3C of hepatitis A virus by site-directed mutagenesis.
[7]
PubMed ID12036580
JournalGene
Year2002
Volume289
Pages19-29
Authorsvan Rensburg H, Haydon D, Joubert F, Bastos A, Heath L, Nel L
TitleGenetic heterogeneity in the foot-and-mouth disease virus Leader and 3C proteinases.
[8]
PubMed ID12377789
JournalJ Biol Chem
Year2002
Volume277
Pages50564-72
AuthorsPhan J, Zdanov A, Evdokimov AG, Tropea JE, Peters HK 3rd, Kapust RB, Li M, Wlodawer A, Waugh DS
TitleStructural basis for the substrate specificity of tobacco etch virus protease.
[9]
CommentsX-ray crystallography
PubMed ID15654079
JournalJ Biol Chem
Year2005
Volume280
Pages11520-7
AuthorsBirtley JR, Knox SR, Jaulent AM, Brick P, Leatherbarrow RJ, Curry S
TitleCrystal structure of foot-and-mouth disease virus 3C protease. New insights into catalytic mechanism and cleavage specificity.
Related PDB2bhg
[10]
PubMed ID16288920
JournalJ Mol Biol
Year2005
Volume354
Pages854-71
AuthorsYin J, Bergmann EM, Cherney MM, Lall MS, Jain RP, Vederas JC, James MN
TitleDual modes of modification of hepatitis A virus 3C protease by a serine-derived beta-lactone: selective crystallization and formation of a functional catalytic triad in the active site.

comments
The enzymes in this entry are parts of genome polyprotein from foot-and-mouth disease virus, which is composed of 4 coat proteins, 3 core proteins, 2 proteases (leader protease, picornain 3C), genome-linked proteins, 3D polymerase.
The tertiary structures for the 4 coat proteins (PDB; 1zba, 1zbe) and a protease (E.C. 3.4.22.28, PDB;2bhg) have been solved to date.
The enzyme (picornain 3C; EC 3.4.22.28) cleaves GLN/GLU-|-GLY/SER/THR bonds in its polyprotein. The catalytic domain strucutre for the peptidase has been solved so far. This protease belongs to the peptidase family-C3, to which picornain 3C from other picornaviruses (M00209, M00217) and picornain 2A (EC 3.4.22.29;M00217) belong.
The catalytic mechanism of this enzyme seems to be similar to that of trypsin (D00197 in EzCatDB), which is its homologous enzyme, although its catalytic site is composed of Cys/His/Asp and mainchain amide groups.

createdupdated
2006-07-112009-02-26
Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/JST (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005-)

© Computational Biology Research Center, AIST, 2004 All Rights Reserved.